Growth Hormone and Counterregulation in the Pathogenesis of Diabetes

Dong, Xuehong; Su, Lei; Patti, Mary‐Elizabeth

doi:10.1007/s11892-022-01488-7

Cited by 5 publications

(8 citation statements)

References 125 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Insulin-like growth factor binding protein 1 modulates IGF-1 bioavailability and has been shown to inhibit IGF-1 effects, which may explain the inverse association between the 2 hormones in our analysis . Insulin-like growth factor binding protein 1, as well as IGFBP-2 through 5, may have IGF-independent associations with glucose uptake and insulin sensitivity and have been associated with the pathogenesis of metabolic syndrome, diabetes, and diabetes complications …”

Section: Discussionmentioning

confidence: 74%

“…43 Insulin-like growth factor binding protein 1, as well as IGFBP-2 through 5, may have IGF-independent associations with glucose uptake and insulin sensitivity and have been associated with the pathogenesis of metabolic syndrome, diabetes, and diabetes complications. 11,12,[44][45][46][47][48][49] JAMA Network Open | Diabetes and Endocrinology…”

Section: Discussionmentioning

confidence: 99%

“…10 Growth hormone signaling may have complex effects on carbohydrate metabolism through several mediators, including insulin-like growth factor-1 (IGF-1), growth hormone receptor (GHR), and IGF binding proteins (IGFBPs). [11][12][13] These GH mediators may directly or indirectly affect body composition, insulin sensitivity, and insulin secretion, potentially influencing the emergence of T2D and its natural history. Thus, our objective was to study associations of GH mediators with measures of glycemic control, insulin sensitivity, and beta cell function, using samples from the TODAY study cohort at baseline and at 36 months-a time point at which most of the cohort had completed puberty and approximately half the participants had a loss of glycemic control.…”

Section: Introductionmentioning

confidence: 99%

“…Puberty is marked by activation of sex hormones and peak secretion of growth hormone (GH) and its effectors . Growth hormone signaling may have complex effects on carbohydrate metabolism through several mediators, including insulin-like growth factor-1 (IGF-1), growth hormone receptor (GHR), and IGF binding proteins (IGFBPs) . These GH mediators may directly or indirectly affect body composition, insulin sensitivity, and insulin secretion, potentially influencing the emergence of T2D and its natural history.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Growth Hormone Mediators and Glycemic Control in Youths With Type 2 Diabetes

Lu,

Wolfs,

El ghormli

et al. 2024

JAMA Netw Open

View full text Add to dashboard Cite

ImportanceYouth-onset type 2 diabetes (T2D) has a more aggressive phenotype than adult-onset T2D, including rapid loss of glycemic control and increased complication risk.ObjectiveTo identify associations of growth hormone mediators with glycemic failure, beta cell function, and insulin sensitivity in youth-onset T2D.Design, Setting, and ParticipantsThis post hoc secondary analysis of the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) randomized clinical trial, which enrolled participants from July 2004 to February 2009, included 398 participants from 15 university-affiliated medical centers with available plasma samples from baseline and 36 months. Participants were youths aged 10 to 17 years with a duration of T2D of less than 2 years who were randomized to metformin, metformin plus lifestyle intervention, or metformin plus rosiglitazone. Participants were followed up for a mean (SD) of 3.9 (1.5) years during the trial, ending in 2011. Statistical analysis was performed from August 2022 to November 2023.ExposurePlasma insulin-like growth factor-1 (IGF-1), growth hormone receptor (GHR), and insulin-like growth factor binding protein 1 (IGFBP-1).Main Outcomes and MeasuresMain outcomes were (1) loss of glycemic control during the TODAY study, defined as hemoglobin A1c (HbA1c) level of 8% or more for 6 months or inability to wean from insulin therapy, and (2) baseline and 36-month measures of glycemia (fasting glucose, HbA1c), insulin sensitivity (1/fasting C-peptide), high-molecular-weight adiponectin, and beta cell function (C-peptide index, C-peptide oral disposition index).ResultsThis analysis included 398 participants (mean [SD] age, 13.9 [2.0] years; 248 girls [62%]; 166 Hispanic participants [42%]; 134 non-Hispanic Black participants [34%], and 84 non-Hispanic White participants [21%]). A greater increase in IGF-1 level between baseline and 36 months was associated with lower odds of glycemic failure (odds ratio [OR], 0.995 [95% CI, 0.991-0.997]; P &lt; .001) and higher C-peptide index per 100-ng/mL increase in IGF-1 (β [SE], 0.015 [0.003]; P &lt; .001). A greater increase in log2 GHR level between baseline and 36 months was associated with higher odds of glycemic failure (OR, 1.75 [95% CI, 1.05-2.99]; P = .04) and lower C-peptide index (β [SE], −0.02 [0.006]; P &lt; .001). A greater increase in log2 IGFBP-1 level between baseline and 36 months was associated with higher odds of glycemic failure (OR, 1.37 [95% CI, 1.09-1.74]; P = .007) and higher high-molecular-weight adiponectin (β [SE], 431 [156]; P = .007).Conclusions and RelevanceThis study suggests that changes in plasma growth hormone mediators are associated with loss of glycemic control in youth-onset T2D, with IGF-1 associated with lower risk and GHR and IGFBP-1 associated with increased risk.Trial RegistrationClinicalTrials.gov Identifier: NCT00081328

show abstract

Section: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Growth Hormone Mediators and Glycemic Control in Youths With Type 2 Diabetes

Lu,

Wolfs,

El ghormli

et al. 2024

JAMA Netw Open

View full text Add to dashboard Cite

show abstract

“…It should also be noted that previous studies suggest a central and peripheral role of IGFBP5 in energy metabolism, with animals lacking Igfbp5 and fed a fatty diet showing glucose intolerance and increased body weight and adiposity [33]. In fact, Igfbp5 expression was speci cally increased in the hypothalamus of male mice fed a high-fat diet without affecting other members of the IGF system [34], and IGFBP5 was altered in the hypothalamus of Pappa2 ko/ko mice of both sexes.…”

Section: Discussionmentioning

confidence: 79%

Sex-based differences in IGF1 signaling pathways in response to PAPP-A2 deficiency

Navarro

López-Gambero

Fernández‐Arjona

et al. 2023

Preprint

View full text Add to dashboard Cite

Background. Patients with pregnancy-associated plasma protein-A2 (PAPP-A2) mutations have progressive postnatal growth retardation and high circulating levels of IGF1 bound in ternary complexes. The present study aims to assess whether Pappa2 deficiency is associated with sex-specific differences in the main components of IGF1 ternary complexes and IGF1 signaling pathways in response to low IGF1 bioavailability. Methods. Plasma, hypothalamus, pituitary gland and liver were analyzed in constitutive Pappa2ko/ko mice of both sexes that have reduced skeletal growth and impaired bone composition. Results. The reduction in body and femur length of Pappa2ko/ko mice was associated with increases in total IGF1 and IGFBP5 concentrations in plasma of females, Igfbp5 mRNA levels in the hypothalamus of males, and Igf1, Igfbp3 and Igfals mRNA levels in the liver of females, suggesting sex- and tissue-specific effects of Pappa2 deficiency on IGF ternary/binary complexes. Pappa2 deficiency was also accompanied by increased pituitary GH concentrations in both sexes. Sex-specific dysregulation of IGF1 signaling pathways was found in Pappa2ko/ko mice with higher phosphorylated forms of AKT, mTOR, GSK3β and ERK1/2 in the female hypothalamus, GSK3β in the male pituitary gland, and PI3K and AMPKα in the female liver, suggesting sex-based alterations in regulators of cell proliferation/growth and protein/glucose metabolism. Conclusions. These data suggest that sex-specific differences in IGF ternary complexes and IGF1 signaling pathways are associated with Pappa2 deficiency, pointing to molecular mechanisms that may participate in the physiopathology of postnatal growth retardation in a sex-dependent manner.

show abstract

Update on diabetic retinopathy during pregnancy

Huang,

Liang,

Huang

et al. 2024

European Journal of Ophthalmology

View full text Add to dashboard Cite

Diabetes mellitus (DM) leads to several vascular and neurological complications, including diabetic retinopathy (DR). As the population ages, health problems in certain groups, including children and pregnant women, are drawing more and more attention. Pregnancy is one of the independent risk factors for the development and progression of DR. Pregnancy-induced changes may contribute to or worsen DR, which can cause a tremendous burden on public health. It is essential for pregnant women with DR and their offspring to minimize the risk of vision loss from DR in this population and adverse outcomes by understanding the development and processes behind this process. Thus, we have updated the recent situation of epidemiology, evolution characteristics, risk factors, pathophysiology, pregnancy outcomes for a better understanding of the latest status of DR, helping to improve maternal and neonatal pregnancy outcomes, and promoting health for women with DR.

show abstract

Growth Hormone and Counterregulation in the Pathogenesis of Diabetes

Cited by 5 publications

References 125 publications

Growth Hormone Mediators and Glycemic Control in Youths With Type 2 Diabetes

Growth Hormone Mediators and Glycemic Control in Youths With Type 2 Diabetes

Sex-based differences in IGF1 signaling pathways in response to PAPP-A2 deficiency

Update on diabetic retinopathy during pregnancy

Contact Info

Product

Resources

About